Beschreibung
While working as a chromatographer in the pharmaceutical industry, it became apparent to the editor that there was a pressing need for a comprehensive reference text for analysts working on the resolution of enantiomers by liquid chromatography (LC). This need arises from the fact that, whereas previously it was very difficult to determine enantiomers by direct means, there is now a wide choice of direct LC methods. At the same time, regulatory authorities have been changing their attitudes towards the administration of pharmaceuticals as racemates, partly because it is now possible to study the individual enantiomers. Clearly this abundance of new information needs to be rationalized. More importantly, the chiral LC systems which are commercially available or readily accessible to the practising chromatographer needed to be reviewed and, to a much greater extent than in existing reviews or books, discussed in terms of their practical application. Accordingly this book is very much orientated towards the practical aspects of these commercially available and readily accessible chiral LC systems. To this end, it is written for practising chromatographers by a team of practising, experienced chromatographers who have spent many years tackling the problems presented by resolving enantiomers by LC. The practical aspects of common chiral LC systems cannot be fully understood if discussed in isolation.
Autorenporträt
Inhaltsangabe1 Introduction.- 1 Molecular asymmetry.- 1.1 Chirality.- 1.2 Chiroptical properties.- 1.3 Asymmetric centres.- 1.4 Twisted structures.- 1.4.1 Cumulenes.- 1.4.2 Spiro compounds.- 1.5 Hindered rotation.- 1.5.1 Atropisomers.- 1.5.2 Ansa compounds.- 1.6 Molecular overcrowding.- References.- 2 The importance of enantiomer separations.- 2.1 Introduction.- 2.2 Enantiomers versus racemates: questions of efficacy and safety.- 2.3 Enantiomers versus racemates: questions of pharmacokinetics.- 2.4 Experimental considerations for investigation of pure enantiomers.- 2.5 Conclusion.- References.- 3 Chiral liquid chromatography: past and present.- 3.1 Historical perspectives.- 3.2 Three-point rule.- 3.3 Development of commercially-available or easily accessible direct chiral resolution methods.- 3.3.1 Chiral ligand exchange chromatography.- 3.3.2 Synthetic multiple-interaction CSPs.- 3.3.3 Protein CSPs.- 3.3.4 Cyclodextrin CSPs.- 3.3.5 Cellulose CSPs.- 3.3.6 Synthetic polymer CSPs.- 3.3.7 Chiral ion-pair chromatography.- 3.3.8 Other direct chiral resolution methods.- 3.4 Present status of chiral liquid chromatography.- References.- 2 Chiral Derivatization.- 4 Chiral derivatization.- 4.1 Introduction.- 4.2 Diastereomer formation.- 4.3 Reagents.- 4.3.1 Acylating reagents.- 4.3.2 Amine reagents.- 4.3.3 Isocyanates and activated carbamates.- 4.3.4 Isothiocyanates.- 4.3.5 Chloroformates.- 4.3.6 Reagents based on o-phthalaldehyde and chiral thiols.- 4.3.7 Other reagents.- 4.4 Separation mechanisms.- 4.5 Detection.- 4.6 Applications.- 4.6.1 Resolution of l-isopropyl-amino-2-propanols (?-blockers).- Acknowledgements.- References.- 3 Direct Chiral Resolution.- 5 Chiral ligand exchange chromatography.- 5.1 Introduction.- 5.2 Immobilized metal coordinating ligands.- 5.3 Metal coordinating ligands as mobile phase additives.- 5.4 Ligand exchange mechanism.- 5.5 Enantiomeric resolution of d and l amino acids.- 5.5.1 Free amino acids.- 5.5.2 Dansyl amino acids.- 5.5.3 Imino acids.- 5.6 Parameters affecting ligand exchange.- 5.6.1 Metal ion.- 5.6.2 Metal to ligand ratio.- 5.6.3 Concentration of metal complex.- 5.6.4 Eluent pH.- 5.6.5 Elution order.- 5.6.6 Organic modifier.- 5.6.7 Stereoselectivity.- 5.7 Conclusion.- References.- 6 Synthetic multiple-interaction chiral bonded phases.- 6.1 Introduction.- 6.2 Survey of multiple-interaction CSPs.- 6.2.1 Historical development.- 6.2.2 Survey.- 6.2.3 Preparation of CSPs.- 6.2.4 General chromatographic considerations.- 6.3 Resolutions of enantiomeric solutes.- 6.3.1 Survey.- 6.3.2 Derivatization of solutes.- 6.3.3 Limitations.- 6.4 Special applications.- 6.4.1 Preparative separations.- 6.4.2 Enantiomeric trace analysis.- 6.4.3 Elution order and configuration.- 6.5 Conclusion.- References.- 7 Immobilized proteins as HPLC chiral stationary phases.- 7.1 Introduction.- 7.2 The AGP-CSP.- 7.2.1 Preparation of the CSP.- 7.2.2 Solute selectivity.- 7.2.3 Mobile phase effects.- 7.2.4 Effect of pH.- 7.2.5 Effect of mobile phase modifiers.- 7.2.6 Applications of the AGP-CSP to pharmacological studies.- 7.3 The bovine serum albumin (BSA) CSP.- 7.3.1 Preparation of the CSP.- 7.3.2 Solute selectivity.- 7.3.3 Mobile phase effects.- 7.3.4 Effect of pH.- 7.3.5 Effect of buffer concentration.- 7.3.6 Effect of mobile phase modifiers.- 7.3.7 Applications of BSA-CSP to pharmacological studies.- 7.4 Chiral phases based on enzymes and other biological polymers.- 7.4.1 Immobilized ovomucoid.- 7.4.2 Immobilized ?-chymotrypsin.- 7.5 Conclusion.- References.- 8 Cyclodextrin inclusion complexation.- 8.1 Structure of cyclodextrin.- 8.2 Mechanism of chiral separation.- 8.3 Inclusion complexes.- 8.4 Examples of chiral separations.- 8.4.1 ?-Cyclodextrin column.- 8.4.2 ?-Cyclodextrin column.- 8.4.3 ?-Acetylated cylcodextrin.- 8.4.4 Aromatic and alkyl groups and their behaviour with cyclodextrin.- 8.5 Choosing conditions for separation.- 8.5.1 Mobile phase effects.- 8.5.2 Salt and pH effects.- 8.5.3 Effect of temperature.- 8.5.4 Effect of flow rate.
Herstellerkennzeichnung:
Springer Verlag GmbH
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E-Mail: juergen.hartmann@springer.com
